Adrenoleukodystrophy (ALD) occurs when certain fats (very long chain fatty acids, or VLCFAs) cannot be broken down in the body. These fats build up and affect how the body normally functions. This disease largely affects the nervous system and adrenal glands. When an individual has ALD, the buildup of VLCFAs may disrupt the fatty covering (myelin) of the nerve cells in the brain and spinal cord causing the myelin to breakdown, which reduces the ability of the nerves to relay information to the brain. Without myelin, the nervous system cannot function properly causing for example difficulties swallowing or weakness in the legs. However these symptoms vary depending on the type and age of onset and other factors which are not well understood. In addition, the build of VLCFAs damages the outer layer of the adrenal glands (adrenal cortex).
Adrenoleukodystrophy (ALD) affects 1 in 17,000 individuals (males and females) worldwide, regardless of race, ethnicity and geography. ALD affects males more severely and is more common in males because it is an X-linked condition. However, 20-40% of women who are carriers have symptoms in adulthood.
Also known as
- X-Linked Adrenoleukodystrophy (ALD)
- Adrenomyeloneuropathy (AMN)
If your baby’s newborn screening result for ALD was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small. However, as a few babies do truly have the condition, it is very important that you take your baby to the follow-up appointment for a confirmatory test. Because the harmful effects of untreated ALD can begin soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve blood testing. The blood test looks at levels of VLCFAs, which are elevated in individuals with ALD. Testing may also include testing for alterations in the ABCD1 gene (see below in Causes). Both of these tests are very accurate tests in males with ALD. Neither the VLCFA level nor the type of genetic alteration predicts the type of ALD the individual develops. In females, the biochemical screening (detecting VLCFA levels) detects 80-85% of female carriers. All carriers are picked up by the genetic testing, but if the woman is the only one being tested with no family members affected or able to be tested, in some cases it is difficult to know if the mutation or change found will cause ALD (sometimes a change in a gene may be harmless).
If the blood test shows that your baby has ALD, your doctor will discuss how to keep your baby healthy. This usually involves monitoring periodically for adrenal insufficiency with a blood test and performing a magnetic resonance imaging scan (MRI) every 6 to 12 months to detect changes due to childhood cerebral disease.
Childhood cerebral form ALD:
- Symptoms can begin as early as age 2 but more commonly between ages 4-10 years old.
- Difficulty swallowing
- Vision problems; crossed eyes
- Hearing loss
- Difficulty reading, writing, understanding speech, and comprehending written and spoken material
- Aggressive behavior
- Adrenocortical insufficiency or Addison’s disease; adrenal glands do not produce enough steroid hormones
- Poor coordination
- Changes in muscle tone; spasms and spasticity
- Worsening nervous system deterioration
- Decreased fine motor control
- Urinary and genital tract disorders
- Progressive stiffness and weakness in the legs (paraparesis)
- Decreased appetite
- Darker areas of skin color or pigment
- Loss of weight and muscle mass
- Muscle weakness
- Low blood sugar
If left untreated, this condition can result in a severe situation referred to as an adrenal crisis.
There are three different typical presentations of ALD.
Boys with childhood cerebral ALD (cALD) usually start showing symptoms when they are between 4 and 10 years old. Symptoms start with attention deficit disorder/hyperactivity and then progress to the symptoms listed under condition characteristics. The condition progresses very quickly, and the child usually passes away a few years after symptoms first appear, although some with intensive medical treatment may survive longer. Recent advances are beginning to change the outlook for boys affected cALD however. The development of cALD may be detected by changes on special imaging called magnetic resonance imaging (MRI) months to years in advance of seeing symptoms. Boys who develop these changes may be referred for effective therapy (see below).
Men with adrenomyeloneuropathy (AMN) start showing symptoms around age 20 years old or older. Most individuals with AMN, but not all, have adrenocortical insufficiency. About 10-20% of individuals this condition will have severe brain and nervous system damage causing an early death. Women who carry ALD may develop similar symptoms.
Adrenal insufficiency or Addison’s disease occurs in 90% of males with ALD and can present as early as 6 months of age. Addison’s disease prevents the body from handling stress, but can be treated with a replacement dose of a corticosteroid taken daily, as well as stress doses when needed. Symptoms can begin anytime from early childhood to adulthood. While it would appear to be less severe than the neurologic presentations, it is a serious condition and requires appropriate medical management. If left untreated, a person affected by Addison disease may go into a coma. Most individuals with Addison disease will go on to develop some neurologic aspects with time.
More than twenty percent of women who are carriers show some symptoms of ALD. These often appear later than in men, but may be as severe. Some women may never show any symptoms. Adrenal insufficiency is not typically seen in women.
Individuals who have adrenal insufficiency need to have regular adrenal gland testing, and can be treated effectively with replacement corticosteroids. The medication replaces what the body would have made daily, but needs to be carefully monitored and adjusted as individuals grow. Illnesses and other stressors such as surgery require increased doses.
Allogeneic hematopoietic cell transplantation (HCT ) or Stem Cell Transplantation
HCT is a treatment that may halt the progression of cALD in children if the disease is diagnosed and treated early. Stem cells are taken from umbilical cord blood or bone marrow from a healthy, matched donor and given to the child with cALD. These new stem cells produce the protein ALDP (explained below) that the child with cALD cannot produce himself. HCT however is a complicated procedure and not without risks.
There is no specific treatment for ALD, Eating a diet low in very long chain fatty acids does not alter the levels in the blood and is not protective.
The compound Lorenzo’s oil does lower VLCFA in the blood. It is considered an investigational agent and its role in altering manifestations of the disease is under study.
Other treatments include medication to help relieve symptoms like stiffness and seizures, and physical therapy, which can help relieve muscle spasms and reduce muscle rigidity.
There is currently a clinical trial for gene therapy which may be another method to stop the progression of ALD.
Children with childhood cerebral ALD (cALD) will have ongoing neurological deterioration. Unless HCT (stem cell bone marrow transplantation) is done early, the child will continue to lose neurologic abilities. Sadly without HCT, most children with cALD will die before age ten. The best results from HCT are seen if the transplant is performed when the beginning changes to the brain are detected by MRI but before physical symptoms are seen.
The other forms of ALD are milder, and will progress over decades. AMN may result in early death due to nervous system deterioration, but Addison disease can be managed through regular testing and treatment with replacement corticosteroid.
Adrenoleukodystrophy is caused by mutations or changes in the ABCD1 gene. This gene provides instructions for making the protein, adrenoleukodystrophy (ALDP), which transports VLCFAs into peroxisomes. Peroxisomes are small sacs inside cells that breakdown VLCFAs and other molecules.
When the ABCD1 gene has a mutation or change, there is not enough ALDP being made, so VLCFAs are not transported and broken down correctly. This causes a build up of VLCFAs in the body, which damages the myelin and the adrenal glands leading to the symptoms seen in ALD.
ALD is inherited in an X-linked pattern, meaning the mutated or changed gene is located on the X chromosome, one of the two sex chromosomes in each cell. Females have two X chromosomes in each cell. Males have one X chromosome and one Y chromosome, so one mutated or changed copy of the ABCD1 gene is enough to cause ALD.
Female carriers of ALD (females with one non-working copy of the gene and one working copy) have been shown to experience the signs and symptoms of ALD more often than expected. Some carriers may show no symptoms, others may have mild symptoms, and others may have more significant symptoms in adulthood.
Support for Adrenoleukodystrophy
Support groups can help connect families who have a child or other family member affected with ALD with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates:
The ALD Alliance offers a Parent's Guide which serves as a source of information, resources, and support for parents of children living with ALD.
Work with your baby’s health care provider to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a physician that specializes in metabolism (the process of breaking down or building molecules in the body), a dietician who can discuss the option of adding Lorenzo’s oil to your child’s diet, and other medical resources in your community.
Some children with ALD have developmental delays. If you think that your baby is not meeting their developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because ALD is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for ALD, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the American College of Medical Genetics and Genomics and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.
At this time we have not located a family story for this particular condition. If your family is affected by ALD and you would like to share your story, please contact us so other families may learn from your experience.
References & Sources
Visit MedlinePlus Genetics for more condition information
Visit OrphaNet for more information on X-linked adrenoleukodystrophy
Visit the New York Times' health guide on ALD
Visit WebMD for more information on Lorenzo’s oil, a treatment used for ALD
Visit Mayo Clinic for more condition information
Visit the National Institute of Neurological Disorders and Stroke for more condition information
Visit The Stop ALD Foundation for more information and resources on ALD
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